Week 5 Flashcards
What kind of response does adrenergic stimulation cause?
Can be excitatory or inhibitory. Epinephrine and norepinephrine causes organs such as the heart, dilatory muscles of iris, and smooth muscles of blood vessels to contract (excite) and causes smooth muscles and other blood vessels to dilate (inhibit). Response is determined by receptor proteins, particularly alpha or beta adrenergic receptors
*What do each of the adrenergic receptors do
alpha 1 : Vasoconstriction in viscera and skin - contraction of smooth muscles
beta 1: Increased heart rate and contractility
beta 2: Dilation (relaxation) of bronchioles (lung) and blood vessels
How do adrenergic receptors act to cause cell response?
All act through G-proteins! Epinephrine/norepinephrine binding causes dissociation of alpha and beta/gamma. Depending on the case, either the alpha or beta/gamma interacts to open/close an ion channel or activate an enzyme.
Beta receptors produce effects through producing cAMP
Alpha receptors produce effects through a rise in cytoplasmic Ca2+ concentration
How does the alpha 2 adrenergic receptor work? What drug acts on these receptors?
Alpha 2 is located on the presynaptic boutons where it produces a decreased release of norepinephrine when activated by norepinephrine in the cleft. This is a negative feedback control over the amount of norepinephrine released.
The most medically important alpha 2 receptors are in the brain. They are stimulated by clonidine and produce a lowering of blood pressure by reducing activation of the entire sympathoadrenal system!
Summarize the fight or flight response
Norepinephrine released by postganglionic sympathetic axons and epinephrine released by adrenal medulla (into blood) boost the ability of the cardiovascular system to respond to physical emergencies.
Alpha adrenergic receptors (sensitive to norepinephrine) stimulate vasoconstriction
Beta adrenergic receptors (sensitive to epinephrine) stimulate increased heart rate and contractility. Also promote vasodilation in appropriate organs to prepare body for physical exertion.
Which neurons are cholinergic (release acetylcholine)? what types of responses do they cause and through which type of receptors?
All somatic motor neurons: always excitatory via nicotinic receptors in skeletal muscles and CNS
All preganglionic (sympathetic and parasympathetic): always excitatory via nicotinic receptors in autonomic ganglia
Most postganglionic parasympathetic: usually excitatory but can be inhibitory via muscarinic receptors in visceral organs
drugs that block ACh receptors
Curare (tubocurarine) blocks nicotinic ACh receptors
Atropine (belladonna) blocks muscarinic ACh receptors
review how the two types of ACh receptors work
Nicotinic: ligand gated ion channel opens when ACh binds and allows Na+ and K+ to flow in/out. Na+ movement is the dominant effect and causes depolarization and excitation.
Muscarinic: coupled to G-proteins which can open or close different membrane channels and activate different enzymes producing either excitation of inhibition.
Most visceral organs receive what type of innervation from sympathetic and parasympathetic systems?
Dual innervation: innervated by both sympathetic and parasympathetic fibers in either antagonistic, complementary, or cooperative ways.
Give 2 examples of antagonistic effects of sympathetic and parasympathetic systems
In the pacemaker region of the heart, adrenergic stimulation from the sympathetic fibers increases heart rate while ACh release from parasympathetic fibers decreases heart rate. The heart rate can therefore be increased by two ways:
- Parasympathetic activity decreases - major determinant, occurs early in exercise
- Sympathetic activity increases - during intense exercise
A reverse of this example is seen in the digestive tract where sympathetic nerves inhibit and parasympathetic nerves stimulate (pretty much the only exception to sympathetic=speed up and para= slow down)
Explain the effects of the sympathetic and parasympathetic systems on the diameter of the pupil of the eye
Sympathetic nerves cause dilation by contraction of the radial muscles
Parasympathetic nerves cause constriction by contraction of the circular muscles
Explain the general features of endocrine glands and which organs are endocrine glands
Endocrine glands lack ducts while exocrine glands have ducts (secrete sweat). Endocrine glands secrete hormones into the blood to interact with target cells containing the specific receptor for the hormone. Many endocrine glands are organs whose primary function is production and secretion of hormones. However, many other organs secrete hormones and so are also considered endocrine glands (like heart, adipose, kidneys)
Sometimes chemical messengers (neurotransmitters) are secreted into blood, especially from the hypothalamus. These are called neurohormones and include norepinephrine, for example.
compare neurotransmitters and hormones
Both involve changes in ion flow and membrane potential. Both must interact with a specific receptor protein to cause a specific sequence of changes and there must be a mechanism to turn off the action (rapid removal or chemical inactivation)
The only main difference is that neurotransmitters do not travel in the blood but instead diffuse across a narrow synaptic cleft.
In fact, the same molecule can serve as both a neurotransmitter AND a hormone!
Give a brief overview of the classifications of hormones
Amines: derived from amino acids tyrosine and tryptophan. Secreted by adrenal medulla, thyroid, and pineal glands
Polypeptides and proteins: distinction is blurry, proteins are just large peptides (over 100 amino acids). ADH is polypeptide (small) while Insulin is messier (2 short peptides joined)
Glycoproteins: consist of protein bound to one or more carbohydrate groups. Includes FSH and LH
Steroids: derived from cholesterol. Includes testosterone, estradiol, progesterone, cortisol. Secreted by adrenal cortex and gonads only
Which hormones are lipophilic/non polar/water insoluble? Where are they made?
Steroid hormones: secreted by only 2 glands, the adrenal cortex and the gonads. Gonads secrete sex steroids while adrenal cortex secretes corticosteroids.
Thyroid hormones: composed of two tyrosines bonded together, if it has 4 iodine molecules it is called tetraiodothyronine, T4, or thyroxine. If it has 3 iodine molecules it is triiodothyronine or T3.
Which hormones are polar/water soluble?
Polypeptides
Proteins
Glycoproteins
Catecholamines (derived from amino acid tyrosine and so are similar to polypeptides)
Explain how polarity of a hormone affects its ability to be deliverable as a drug
Nonpolar hormones can be taken as oral pills because they can pass through the cell membrane. Birth control pills (steroid hormones) and thyroid hormone pills (for hypothyroid treatment) are oral drugs.
Polar hormones cannot be taken orally because they would be digested before being absorbed in the blood. Polypeptides and glycoproteins must be injected
Can melatonin be taken orally?
Melatonin, derived from amino acid tryptophan, can pass through plasma membranes despite its similarities to the polar hormones. It can be take orally
Features of receptor proteins
Specificity
Affinity (high bond strength)
Low capacity - there’s a limited number of receptors per target cell so saturation is possible
How are lipophilic and water soluble hormones transported to target cells?
water soluble are transported in the blood because they can dissolve in the aqueous portion.
lipophilic cannot dissolve in blood so are transported by plasma carrier proteins which they dissociate from to enter the plasma membrane.
What type of proteins are lipophilic hormone receptors? what do they cause in the cell?
They are Nuclear Hormone Receptors because they are within the cell nucleus where they activate genetic transcription by functioning as Transcription Factors. The altered mRNA production directs protein synthesis and changes metabolism of the target cell.
This is called Genomic Action:
steroid hormone enters cell and binds receptor in cytoplasm. It translocates to the nucleus and binds to Hormone Response Elements in the DNA, stimulating transcription
What is tamoxifen and what does it tell us about the effects of hormones
a Selective Estrogen Receptor Modulator (SERM) which acts like estrogen in one organ while antagonizing estrogen in another. Demonstrates that organ response to a hormone is variable based on regulatory proteins called coactivators and corepressors which regulate transcription factors
*Explain the major hormone secreted by the thyroid gland vs the active thyroid hormone
Major hormone is Thyroxine or Tetraiodothyronine (T4). Thyroxine travels in blood attached to carrier proteins called thyroxine-binding globulin (TBG). There is only a small amount of Triiodothyronine (T3) made by the thyroid. Carrier proteins have a high affinity for T4 so unbound T3 is very high. Only free thyroxine and T3 can enter target cells (the carrier bound molecules serve as a reservoir). Once free T4 passes into the cell, it is converted to T3. So, it is T3, not T4, which is the active thyroid hormone in target cells! T3 uses non-specific stepping stone proteins to enter the nucleus and bind its receptor, which is always in the nucleus.
*Why does it take a few weeks for symptoms of hypothyroidism to set in?
There is a reservoir of thyroxine (T4, tetraiodothyronine) contained in the blood on thyroxine-binding globulin carriers. The reservoir allows thyroid hormone to still exert its effect for a while after the thyroid is removed.
What mediates the actions of polar hormones (catecholamines, polypeptides, glycoproteins)? Explain one important pathway
Since they cannot pass through the membrane, they must act through second messengers such as cAMP and Ca2+. cAMP pathway:
Epinephrine/norepinephrine bind to B-adrenergic receptors
G protein dissociates into alpha and beta/gamma
alpha moves through membrane and activates Adenylate Cyclase
ATP is catalyzed to cAMP and two inorganic phosphates (pyrophosphate)
cAMP activates protein kinase to phosphorylate different proteins and activate/inactivate
cAMP is inactivated by *Phosphodiesterase which hydrolyzes it to stop stimulation
*How does Viagra work
Viagra, or Sildenafil, inhibits phosphodiesterase-5 to stop breakdown of cGMP (analogous to cAMP). This prolongs the signal transmitted by cGMP (normally nitric oxide stimulates cGMP to cause vasodilation of smooth muscle). The result is prolonged relaxation/vasodilation of vascular smooth muscles in the penis and erection is easily achieved and maintained.
2 (and kind of third) main areas of the pituitary gland (hypophysis) and their embryonic origins
Anterior Lobe or Adenohypophysis: derived from Rathke’s pouch that migrates upward from embryonic mouth - has NO direct brain connection
Posterior Lobe or Neurohypophysis: derived from down growth of the brain
Infundibulum: stalk like structure connects to hypothalamus
what structure of the pituitary gland is only present in fetus
pars intermedia. A strip between the anterior and posterior lobes. The cells mingle with the anterior lobe and are no longer a separate structure in adults
What hormones are secreted by the anterior pituitary (pars distalis of the adenohypophysis)
Trophic Hormones (trophic means feed - these hormones cause hypertrophy to organs)
- Growth Hormone (GH or somatotropin): promotes overall tissue/organ growth
- Thyroid Stimulating Hormone (TSH or thyrotropin): stimulates thyroid to secrete T4 and T3
- Adrenocorticotropic Hormone (ACTH or corticotropin): stimulates adrenal cortex to secrete glucocorticoids like cortisol
- Follicle Stimulating Hormone (FSH or folliculotropin): growth of ovarian follicles (female) and sperm cells (male)
- Luteinizing Hormone (LH or luteotropin): ovulation and conversion of ovarian follicle to corpus leteum (female) and secretion of male sex hormones from Ledyig cells (male)
- Prolactin (PRL): stimulates milk production (female) and supports regulation of male reproductive system and kidneys
What hormones are secreted by the posterior pituitary (pars nervosa of the neurohypophysis)? Note the origin of these hormones!
Both are produced by the paraventricular nuclei and supraoptic nuclei of the hypothalamus!
- Antidiuretic Hormone (arginine vasopressin): stimulates water retention by kidneys and decreased urination as well as a rise in blood pressure (“pressor” effect)
- Oxytocin (drug from is Pitocin): stimulates contractions of the uterus during labor, necessary for parturition (birth). Also stimulates contractions of mammary gland resulting in milk-ejection reflex. Other roles in sexual arousal, mother-infant bonding, trust, social cues, and love
Hormones of the pars intermedia (Didn’t talk about in class, but is in notes)
Pars intermedia doesn’t exist in adult humans, but in infants and animals it is thought to secrete melanocyte-stimulating hormone (animals) and pro-opiomelanocortin (humans) which is a pro hormone that forms beta-endorphin, MSH, and ACTH. Elevated secretions of ACTH cause a darkening of skin
Describe the pathway of the posterior pituitary hormones from production to secretion. Give examples of when the hormones are released
ADH and Oxytocin are produced in the hypothalamus in the supraoptic and paraventricular nuclei. They are transported along axons of the hypothalamo-hypophyseal tract to the posterior pituitary where they are stored and later released in response to a neuroendocrine reflex
In nursing mothers, mechanical stimulation of suckling acts, via sensory nerve impulses to the hypothalamus, to stimulate the reflex secretion of oxytocin and causes milk secretion.
ADH secretion is stimulated by osmoreceptors in the hypothalamus in response to a rise in plasma osmolality. This stimulates thirst and release of ADH to decrease urination. ADH secretion can be inhibited by stimulation from the heart when there is a rise in blood volume.
why is the anterior pituitary NOT the master gland?
Secretion of the anterior pituitary’s hormones is controlled by the hypothalamus, which is controlled by other stimuli. So while the hormones of the anterior pituitary are many, and do effect a lot of organs, it is not the “master”. It does not control the secretion of these hormones
Describe the pathway of the release of hormones from the anterior pituitary
The anterior pituitary is controlled by hormonal regulation, not neural. The hypothalamus produces releasing and inhibiting hormones that are transported to the median eminence, which contains blood capillaries drained by venues in the stalk of the pituitary. The venues deliver blood to a second capillary bed in the anterior pituitary. The vascular link between the median eminence and the anterior pituitary forms a Portal System. So, the pathway between the hypothalamus and anterior pituitary is called the Hypothalamo-Hypophyseal Portal System.
Thyrotropin-releasing Hormone (TRH) from hypothalamus stimulates secretion of TSH from anterior pituitary
Corticotropin-releasing Hormone (CRH) from hypothalamus stimulates secretion of ACTH from anterior pituitary
Gonadotropin-releasing Hormone (GnRH) from hypothalamus stimulates secretion of FSH and LH from anterior pituitary.
Growth Hormone Resealing Hormone (GHRH) stimulates growth hormone release and Somatostatin inhibits growth hormone release
Dopamine (Prolactin Inhibiting Hormone) inhibits prolactin secretion
Describe the negative feedback effects on trophic hormones
Anterior pituitary secretion of ACTH, TSH, FSH, and LH is controlled by negative feedback inhibition from their target glands. ACTH is inhibited by a rise in corticosteroid secretion, TSH by a rise in thyroxine secretion, and FSH/LH by steroid hormones testosterone and estradiol. Removal of the organs that secrete these hormones (adrenals, thyroid, and gonads) causes a rise in ACTH, TSH, FSH, and LH.
Effect occurs at 2 (3?) levels:
1. target gland hormones act on hypothalamus to inhibit secretion of releasing hormones
2. target gland hormones act on anterior pituitary to inhibit response to releasing hormones
(3?) short feedback loops occur where trophic hormone inhibits secretion of its releasing hormone from hypothalamus
Describe the positive feedback effects of trophic hormone release
Only occurs in the menstrual cycle when rising estradiol from ovaries stimulates anterior pituitary to secrete LH, resulting in ovulation. Later in the cycle estradiol has the opposite effect and inhibits LH. Women are complicated
How do emotions affect the pituitary-gonad axis
The axis is stimulated by GnRH from the hypothalamus which receives input form higher brain centers, such as emotion centers! Intense emotions, especially stress, are known to alter ovulation/menstruation timing. There is also a connection between the olfactory center to the GnRH producing neurons of the hypothalamus, thus smell can influence GnRH secretion and affect reproductive functioning. (Vomeronasal organ stimulated by airborne hormones - pheromones. also causes dormitory effect or synchronizing of cycles)
Describe the embryonic origins of the adrenal gland and how this relates to stimulation of the gland
Adrenal Medulla is derived from embryonic neural crest ectoderm while Adrenal Cortex is derived from mesoderm. Therefore, the adrenal medulla has a direct neural connection and the pheochromocytes (chromatin cells) of the gland secrete catecholamine hormones (epinephrine and a little norepinephrine) into the blood in response to preganglionic sympathetic axons. The adrenal cortex, however, is controlled hormonally by ACTH secretion from anterior pituitary
Three zones of the adrenal cortex and what they secrete (and function of secretions)
Outer zona glomerulosa: secretes mineralocorticoids (aldosterone) which regulate Na+ and K+ balance
Middle zone fasciculata: secretes glucocorticoids (cortisol) which regulate metabolism of glucose and other molecules
Inner zona reticularis: secretes weak androgens (dehydroepiandrosterone DHEA and androstenedione) which supplement sex steroids and are the only source of testosterone in females and contribute to their sex drive, function not well understood.
These are all steroid hormones and made from cholesterol
What does aldosterone do
Aldosterone is the most potent mineralocorticoid (produced in zona glomerulosa) and stimulates kidneys to retain Na+ and water while excreting K+ into urine. This increases blood volume and pressure and regulates blood electrolyte balance.
Antidiuretic hormone is the other main controller of blood volume/pressure. It causes decreased urination for higher water retention in the body
What does cortisol do
Cortisol (hydrocortisone) is the predominant glucocorticoid (secreted by zona fasciculata). Secretion is caused by ACTH from anterior pituitary during stress. Effects include stimulation of protein degradation, gluconeogensis, inhibition of glucose utilization, increase in blood glucose, and lipolysis to release free fatty acids into blood. This provides more energy molecules in the blood for use during stressful times.
What are exogenous glucocorticoids? What are they useful for and what side effects do they cause
Used to suppress immune response and inhibit inflammation, good for treating inflammatory diseases. Side effects include hyperglycemia, decreased glucose tolerance, decreased collagen and other ECM protein synthesis, and increased bone resorption leading to osteoporosis
What hormones are released by the adrenal medulla and what is their effect
Pheochromocytes of the adrenal medulla secrete epinephrine and some norepinephrine. Similar effect as they cause in the sympathetic nervous system but lasts 10 times longer. Increases cardiac output, heart rate, dilates blood vessels, increases mental alternates, increase respiratory rate, and elevate metabolic rate
Preganglionic sympathetic axons of the Splanchnic Nerve innervate the adrenal medulla to secrete its hormones during fight or flight. The sympathoadrenal effects support a rise in blood glucose (stimulates gluconeogenesis) and fatty acids (stimulates lipolysis
What common effect produced all of the symptoms observed by Hans Selye
Stress, more specifically activation off the pituitary-adrenal axis. Increased secretion of ACTH causes increased secretion of glucocorticoids (cortisol)
*Describe the General Adaptation Syndrome (GAS)
produced by stress, has three stages:
- alarm reaction: adrenal glands activated in fight or flight response
- stage of resistance: secretion of CRH from hypothalamus and ACTH from anterior pituitary and corticosteroids from adrenal cortex promote readjustment to stressor
- stage of exhaustion: if readjustment is not complete, sickness and even death may occur
Why is the GAS response needed
Cortisol inhibits the immune system and thereby reduces damage due to inflammation. So severe trauma that triggers immune response requires cortisol to limit that immune response and avoid making things worse.
look up the hormones released by paraventricular nucleus, he seemed very excited whenever one came up
oxytocin, vasopressin (ADH), orticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone
What axis becomes more active with chronic stress and feelings of being passive/out of control
Hypothalamus-anterior pituitary-adrenal axis. Hypothalamus (paraventricular nuclei) secretes corticotropin-releasing hormone which stimulates anterior pituitary to secrete adrenocorticotrophic hormone whit stimulates adrenal cortex to secrete glucocorticoids.
What are the physical effects of chronic stress? what about positive stress?
Negative stress (distress): poor recovery from illness, tumor growth, anxiety, social aversion Positive stress (eustress): heath and recovery from illness, strong social interactions
How does stress affect memory
Memory regions of the brain have receptors for stress hormones and both promote AND suppress long-term potentiation and depression in memory.
Glucocorticoids and epinephrine enhance LTP and memory formation during acute stress and bolster consolidation to long term memory. Emotionally charged memories are more likely to be remembered long term.
Glucocorticoids also hinder retrieval of memories making them harder to recall. may also act on amygdala to contribute anxiety and depression associated with stress
NOTE: glucocorticoids have been used to suppress retrieval of emotional memories in PTSD patients!
How is a metabolic disorder caused by chronic stress
Glucocorticoids lead to a rise in blood glucose (“stress hyperglycemia”) and stimulate catabolism break down of protein and fat. Thus, they antagonize actions of anabolic hormones such as insulin. Chronic stress therefore causes insulin resistance - reduced sensitivity of target tissues to insulin - and subsequent type 2 diabetes mellitus. Also contributes to “metabolic syndrome” which is an apple shaped obesity (more on this later?)
Describe the structure of the thyroid gland, name all the parts and secretions
Two lobes connected by the isthmus. The largest of the purely endocrine golds. Consists of spherical hollow sacs called thyroid follicles lined with epithelium composed of follicular cells that synthesize Thyroxine (T4) the main thyroid hormone. Interior of the follicles contain colloid. There are also parafollicular cells that secrete calcitonin (thyrocalcitonin)
Describe the structure of the formation of Sertoli cells and what this contributes to the germinal cells
Sertoli cells form a continuous layer connected by tight junctions around the circumference of each tubule. This constitutes a blood-testes barrier where molecules from blood must first pass through Sertoli cells to get to germinal cells. This barrier prevents the immune system from destroying the sperm.
As the Sertoli cells extend into the lumen of the tubule, they have complex cup-shaped processes that envelope the developing germ cells. All developing spermatocytes, spermatogonium, and spermatids are surrounded by Sertoli cytoplasm.
*Describe the Immunologically Privileged Site that is the seminiferous tubules
Formed by Sertoli cells, the blood-testes barrier helps prevent immune attack on the sperm by producing FAS ligand which binds to T lymphocytes and causes apoptosis. If sperm were to escape the privileged site due to injury, Autoimmune Sympathetic Orchitis would occur where the immune system destroys BOTH testes in response to detecting the sperm antigens from one.
How is sperm cytoplasm removed
By phagocytosis by Sertoli cells on the “residual bodies” of the cytoplasm from the spermatids. This also may transmit regulatory molecules from germ cells to Sertoli cells and the provision of molecules from the sertoli to the germ. For example, the X chromosome is inactive during meiosis, but contains necessary genes, so Sertoli cells provide those molecules while it is inactive.
What causes testosterone to be concentrated in the tubules
Sertoli cells secrete Androgen-Binding Protein into the seminiferous tubules which binds and concentrates testosterone. ABP production is stimulated by FSH and receptors for FSH are only found in Sertoli cells, thus all effects of FSH in the testes must be mediated by Sertoli cells. Effects would include ABP production, spermatogenesis, and more
Describe the structure of a spermatozoon
Head: contains nucleus and DNA
Acrosome: important cap on the head
Flagellum tail: has characteristic 9+2 microtubule structure called an Axoneme
axoneme is divided into three parts:
Upper Midpiece: fibrous sheath and mitochondria around axoneme
Principal piece: only fibrous sheath around axoneme
End piece: only axoneme
When does spermatogenesis complete and what triggers its completion
Primary spermocytes and entry into early meiosis begin in embryo, but it is arrested until puberty when testosterone secretion rises. Testosterone is required for completion of meiosis and maturation. Likely it is derivatives of testosterone (5a-reduced androgen AND estrogen) that actually cause maturation. Testosterone is secreted by Leydig cells under LH stimulation. FSH is not required for spermatogenesis, but does enhance the effects of LH (which IS required). Without FSH, spermatogenesis would commence later in puberty and would produce less sperm, but would still be fertile.
Where do sperm travel and store before any sexual response occurs
Formed in seminiferous tubules then are moved to the Rete Testis and drained via efferent ductules into the Epididymis. From the head of the epididymis, sperm are drained from its tail by a single Ductus Deference (Vas Deferens). Spermatozoa are NONMOTILE at this point due to low pH of epididymis fluid. They are stored and mature in the epididymus.
when do sperm become motile
During ejaculation the pH is neutralized by alkaline prostatic fluid and some motility is gained. Full motility occurs only after they enter the female reproductive tract
Where do sperm travel during a sexual response
From the epididymis, sperm are barred via the ductus deferens out of the scrotum into the pelvic cavity. The seminal vesicles then add secretions at the point where the ductus defers becomes an ejaculatory duct. It quickly enters the Prostate (which adds secretions) and soon merges with the Urethra. The fluid is known as semen now
What is contained in the fluid accompanying ejaculation
Several secretions are added as sperm travels from epididymis to urethra for ejaculation.
- Seminal vesicles add seminal fluid: contains prostaglandin that cause uterus to contract (propels sperm to Fallopian tubes). also contains fructose for energy source as spermatozoa travels (seminal vesicle fluid is 60% of semen volume!)
- Prostate adds secretions that contain citric acid, calcium, and vasiculase enzyme which causes semen to coagulate after ejection (fibrinolysis reverses coagulation to restore more liquid form later)
- Bulbourethral glands (Cowper’s glands) add secretion early in sexual stimulation that lubricates urethra and makes seminal fluid gelatinous
what is benign prostatic hyperplasia, how is it treated
The growth of the prostate can constrict the urethra, increasing the resistance to flow and slowing urination. Drug treatments for BPH usually begin with α1-adrenergic receptor blockers, which cause smooth muscle relaxation in the prostate and the neck of the bladder, promoting urination. 5α-reductase inhibitors reduce dihydrotestosterone and reduce size of the prostate by inhibiting the enzyme that converts testosterone to DHT. (Because DHT acts on hair follicles to promote male-pattern baldness, 5α-reductase inhibitors are also used to treat androgenic alopecia, or male hair loss.) There are also surgical options, including transurethral resection of the prostate (TURP) and transurethral needle ablation (TUNA)
what are some Beta blockers and what do they do
Beta blockers are drugs that act as beta-adrenergic receptor antagonists. Propranolol is nonselective for β1- and β2-adrenergic receptors. Atenolol is relatively selective for the β1-adrenergic receptors in the heart and so is used to lower heart rate and blood pressure in patients with hypertension (high blood pressure). Because the smooth muscle of the bronchioles (airways) in the lungs has β2-adrenergic receptors, a drug that blocks these could reduce the bronchodilation effect of epinephrine. This causes bronchoconstriction making breathing difficult (causes asthma).
what are some alpha agonists and how do they work
The alpha agonist drugs phenylephrine and pseudoephedrine are used in cold medicines to stimulate the α1-adrenergic receptors in the nasal mucosa, promoting vasoconstriction that relieves nasal congestion but can also raise blood pressure (promotes vasoconstriction). Clonidine is an α2-adrenergic receptor agonist that acts in the CNS to reduce the activity of the sympathoadrenal system, thereby promoting vasodilation and lowering the blood pressure.
Asthma caused by and helped by
can be provoked by atenolol, a blood pressure medication, that also causes bronchoconstriction making breathing difficult
Asthmatics used to inhale epinephrine as a beta agonist to stimulate the β2-adrenergic receptors and promote bronchodilation, but this also stimulated the β1-adrenergic receptors in the heart and raised blood pressure. Now people with asthma use inhalers containing more selective β2-adrenergic receptor agonists, such as salbutamol (Albuterol), terbutaline, and others.
how does atropine (atropa belladonna) work? what medical purposes is it used for? cosmetic purpose?
Atropine, from the deadly nightshade plant (Atropa belladonna), is a specific antagonist of the muscarinic ACh receptors, and thus effects of postganglionic parasympathetic axons. It is infused on the eyes to inhibit the muscle contraction that constricts the pupils, resulting in pupil dilation for eye exams. Women during the Middle Ages used this effect to make their eyes more attractive. In addition, atropine can be used to block the vagus nerve-induced slowing of the heart, helping to treat bradycardia (a slow heart rate) and AV node heart block. Atropine is used to reduce the production of saliva and mucus (sometimes before general anesthesia), and to inhibit spasmodic contractions of the intestine and the stomach acid secretion of gastritis. Atropine is also used as a treatment for nerve gas and organophosphate pesticide poisoning, because these toxins can inhibit acetylcholinesterase (AChE) to dangerously increase cholinergic transmission.
describe the cause and danger of autonomic dysreflexia
Autonomic dysreflexia occurs in people with spinal cord injuries at or above the sixth thoracic level (T6). After some time, the reflexes below the injury appear in an exaggerated state. A noxious sensory stimulus—usually from the urinary bladder or colon—can evoke a strong response from the sympathoadrenal system. Sympathetic nerves cause vasoconstriction and increased heart rate, which raise the blood pressure. Pressure receptors in arteries sense this, and send signals via cranial nerves IX and X to the brain. In response, the brain directs an inhibition of sympathetic activity and an increase in parasympathetic activity, which normally maintain homeostasis. But, if the person has a spinal cord injury at or above T6, the inhibition of the sympathetic (thoracolumbar) response cannot descend below the injury. High sympathetic nerve activity below the level of the injury = vasoconstriction = dangerous hypertension, cold skin, goose bumps. Low sympathetic nerve activity above the level of the injury + increased parasympathetic nerve effects = bradycardia (a slow heart rate), nasal congestion, and a flushed, sweaty skin. The bradycardia is insufficient to lower the dangerously elevated blood pressure, and so autonomic dysreflexia requires efforts to eliminate the noxious stimulus that provoked it, as well as other measures.
what are biofeedback techniques? how do they work?
using biofeedback techniques, a person can be trained to have limited but significant control over some autonomic responses. This training involves the use of devices that monitor body changes; for example, devices can monitor brain waves (electroencephalograph or EEG), muscle tension (electromyography, or EMG), skin conductivity (affected by sweating and monitored by GSR—galvanic skin response), and others. Autonomic functions may be trained to help control blood pressure, chronic pain, headache, urinary incontinence, anxiety, and other conditions.
how is pulse rate controlled
vagus (X) nerve (parasympathetic system) uses ACh to slow down pulse
adrenergic (sympathetic system) signals speed up pulse
effects of anabolic steroids in men, women, both, and adolescents
both: Androgens used to promote protein synthesis in muscles. Common side effects: acne, aggressiveness, cholesterol high, liver disease/cancer
side effects in men: Because the testosterone is often converted to estrogen men develop breasts (gynecomastia), baldness, and large prostate. High testosterone inhibits FSH and LH causing testis atrophy and reduce sperm count.
side effects in women: masculinized, reduce fat, coarse skin, increase body growth, hair growth, clitoris growth, deepen voice
adolescents; premature closing of bone growth, cessation of growth
Common targets of treatment in breast cancer and how they work
Estrogen receptor (ER) is common in breast cancers. Standard treatment for postmenopausal breast cancer patients who are ER positive is an aromatase inhibitor that blocks the ability of aromatase to convert testosterone into estradiol. Premenopausal patients who are ER positive also receive tamoxifen—a selective estrogen receptor modulator (SERM). SERMs have an anti-estrogenic effect in the breast, but promote estrogen actions on bone and the endometrium of the uterus.
Some cancers have Her2 (human epidermal growth factor receptor 2) receptor. The Her2 receptors can be blocked by monoclonal antibodies in a drug called Herceptin. The Herceptin antibodies contain an antigen-binding portion produced by mice attached to human immunoglobulin.
what are some methylxanthines and what do they do
Methyxanthines (theophylline caffeine) inhibit phosphodiesterase. Theophylline is sometimes used as a supplementary treatment for asthma, if the person is already taking an inhaled β2-agonist drug (promoting bronchodilation) and a corticosteroid to reduce inflammation. Theophylline inhibition of phosphodiesterase raises the cAMP levels in the cell, enhancing the stimulation of cAMP production by epinephrine’s activation of the β2-adrenergic receptors in the bronchioles and promoting bronchodilation. However, raising cAMP levels in myocardial cells duplicates epinephrine action in the heart, causing increased cardiac rate and strength of contraction. Theophylline also has anti-inflammatory effects.
disorders caused by inappropriate growth hormone secretion
Dwarfism: short stature produced by inadequate secretion of growth hormone (GH) during childhood, often accompanied by deficiency in the other anterior pituitary hormones. Treated with injections of recombinant growth hormone.
Gigantism: caused by oversecretion of GH during childhood, usually the result of an adenoma (a benign tumor) of the anterior pituitary.
Acromegaly: oversecretion of GH during adulthood. Cannot cause further growth in height because the epiphyseal plates of cartilage that produce this growth have closed (changed to bone). Instead, it produces the disfigurement characteristic of acromegaly (chapter 19; see fig. 19.17). Oversecretion of GH for both gigantism and acromegaly can be treated with somatostatin, a hypothalamic hormone that inhibits GH secretion (as discussed shortly), or by surgery.
what is pitocin
Pitocin is an oxytocin injection given to a pregnant woman to hasten a vaginal delivery. Oxytocin receptors become more plentiful in the myometrium (smooth muscle of the uterus) during pregnancy to promote more forceful contractions. Injected oxytocin may be necessary if the fetal membranes have prematurely ruptured, if there is Rh incompatibility, or if there is preeclampsia (pregnancy-induced hypertension). Oxytocin may also be injected into the mother postpartum (after delivery) to minimize hemorrhage.
describe production of thyroid hormones
Iodide accumulates in thyroid follicles and is attached to tyrosine to form thyroglobulin. if one iodine is attached = monoiodotyrosine (MIT), if 2 attached = diiodityrosine (DIT). Two DIT coupled together = tetraiodothyronine/T4/thyroxine. One MIT plus one DIT = triiodothyronine/T3. Then they enter the blood either by binding protein of free T3
Functions of thyroid hormones
stimulate protein synthesis
promote nervous system maturation
increase cell respiration = heat up body
elevates basal metabolic rate (resent rate of caloric expenditure)
remember that thyroid hormones are non polar and activate receptors inside the cell
What hormones effect calcium levels
Parathyroid hormone: the only hormone secreted by the parathyroid glands and the single most important hormone controlling blood calcium concentration. Causes a rise in blood calcium by acting on bones, kidneys, intestine. insufficient PTH = hypocalcemia tetany (body shakes, continuous muscle contraction)
Calcitonin: secreted by parafollicular cells of thyroid and inhibits osteoclast activity, stimulates urinary excretion of Ca2+ by kidneys, lowers blood calcium. HOWEVER, has negligible importance in normal physiology!
how is thyroid cancer treated
Papillary thyroid carcinoma is treated by thyroidectomy (removal of thyroid) and radioactive iodine treatment. Follicular cells take up the iodine and the radioactivity kills the thyroid.
What disorder occurs when thyroid stimulating hormone is inappropriately secreted
Iodine Deficiency (Endemic) Goiter: absence of dietary iodine causes insufficient T4 and T3 production and an overproduction of thyroid stimulating hormone (no negative feedback) which causes overgrowth of the thyroid. common in places with no iodized salt/ seafood
Hypothyroid: caused by inadequate TSH secretion (or a thyroid gland defect, insufficient thyrotropin-releasing hormone release, or insufficient iodine in diet) to cause abnormally low thyroid hormone secretion. Results in a low basal metabolic rate, weight gain, lethargy, decreased ability to adapt to cold, and Myxedema (swelling of hands, feet, face, and eye tissue)
what is the result of iodine deficiency in children
Low thyroxine, as a result of low iodine, causes cretinism which is a severe intellectual disability. Thyroxine is needed for development of the central nervous system and is especially crucial in young children.
what is the endocrine portion of the pancreas called
Pancreatic islets or Islets of Langerhans
the islets contain alpha (glucagon secreting) and beta (insulin secreting) cells which regulate metabolism
Describe the structure and action of insulin
Begins as larger polypeptide called proinsulin which is cleaved into two chains (C protein is released) which are joined.
Insulin acts to LOWER blood glucose. After a meal (rise in blood glucose) the beta cells of the pancreatic islets secrete insulin. Insulin binds to membrane receptors and causes GLUT4 carrier proteins to translocate to the membrane. GLUT4 promotes facilitated diffusion of glucose into the cells. Insulin also activates glycogen synthetase to convert glucose into glycogen for storage.
Describe the function of glucagon
Glucon is secreted by alpha cells of the pancreatic islets and promotes a RAISE in blood glucose. Stimulated by a fall in plasma glucose and a fall in insulin (occurs when person is fasting) glucagon signals liver to hydrolyze glycogen into glucose (glyconeogenesis) which is secreted into blood. Glucagon also stimulates gluconeogenesis where glucose is produced from other molecules to raise plasma glucose. Lipolysis and ketogenesis also occur to provide fatty acids and ketone bodies for energy
what hormone does the pineal gland secrete? what regulates its secretion?
Pineal gland secretes Melatonin. The suprachiasmatic nucleus of the hypothalamus regulates pineal secretion of melatonin through sympathetic neurons. The SCN regulates the body’s circadian rhythms. Light acts through the retinohypothalamic tract (via a retinal pigment called Melanopsin produced by ganglionic cells - not the rods and cones) to entrain rhythms in the SCN to the light/dark cycles. Daylight (blue light) inhibits pineal secretion of melatonin - that’s why blue light from electronics are bad late at night.
what other functions may melatonin have besides sleep cycles?
Melatonin helps regulate time of births in seasonally breeding animals via the pituitary-gonad axis. This is not proven to apply in humans, however excessive melatonin secretion is associated with a delay in onset of puberty. Decreased melatonin contributes to the onset of puberty (controversial)
describe treatment for seasonal affective disorder
phototherapy uses bright fluorescent lamps to act like sunlight and inhibit melatonin secretion, treating seasonal affective disorder. Suggests that depressed mood of SAD involves the retinal ganglion cells that produce the light sensitive pigment melanopsin
what hormones are produced by the gonads and placenta
Testes: androgens - testosterone
Ovaries: estrogen -estradiol-17B, and progesterone
Placenta: estrogen and progesterone and Human Chorionic Gonadotropin (hCG) which is similar to LH and somatomammotropin which is similar to prolactin/growth hormone. Pregnancy tests use human chorionic gonadotropin!
